7H-Pyrrolo[3,2-f]quinazoline-1,3-diamine (Compound 1 herein) and its derivatives, originally synthesized as antifolates in the 1970s (U.S. Pat. No. 4,118,561, (1978); incorporated by reference herein) have been shown to possess a variety of biological activities including antibacterial, anticancer and antiparasitic activity (Gamo F J et al, Nature 465, 305-310 (2010); Kuyper L F et al, J Med Chem 39, 892-903 (1996); Li Q et al, Antimicrob Agents Chemother 51, 2898-2904 (2007); all of which are incorporated by reference herein). Antiviral activity against herpes simplex virus (HSV) has also been reported (Dicker I B et al, Antiviral Res 28, 213-224 (1995); incorporated by reference herein).
The biochemical targets for these compounds include dihydrofolate reductase (DHFR) from various species, thrombin receptors, and protein tyrosine phosphatase 1B (PTP1B) McCormack J J et al, Biochem Pharmacol 28, 3227-3229 (1979); Ahn H S et al, Bioorg Med Chem Lett 9, 2073-2078 (1999) Nadal-Wollbold F, Eur J Pharmacol 644, 188-194 (2010); WO 2004101568 (2004); Cheung A W et al, Bioorg Med Chem Lett 22, 7518-7522 (2012); all of which are incorporated by reference herein.) The wide spectrum bioactivity of Compound 1 is specific because a survey of the target-based and phenotypic screening assays involving Compound 1 in PubChem (http://pubchem.ncbi.nlm.nih.gov/) show it is only active in 35/528 or 6.6% of the assays suggesting that this particular chemotype is a privileged scaffold that is intrinsically useful for different biological targets (Evans B E et al, J Med Chem 31, 2235-2246 (1988) and Welsch S A et al, Curr Opin Chem Biol 14, 347-361 (2010), both of which are incorporated by reference herein).